Genetic counseling: Neurofibromatosis - Type 2
Neurofibromatosis - Type 2 Contracting *How have things been since your last visit? *What questions or concerns would you like us to address today? Etiology *Disease characteristics **Genetic disorder that causes tumors to grow on various nerves **Also affects other tissues such as bones and skin **Two distinct types: NF-1 and NF-2 *Inheritance **Autosomal dominant **Affected individuals have 50% chance of passing on mutation to each of their children **Half of affected individuals have de novo mutations **If neither parent has NF2, recurrence risk is very low - only one case of germline mosaicism reported **Uniform age of onset within families *Molecular genetics **Caused by mutation in the NF2 gene **Located at 22q12 **Normal gene product is schwannomin or merlin ***Homology to 4.1 family of cytoskeletal associated proteins ***Has role in prevention of schwannoma formation ***Tumor suppressor gene *Incidence is 1 in 40,000 people Clinical Features and Natural History *Some variability in clinical manifestations **Variability within families is low **Suggests strong genotype-phenotype correlation *Average age of onset of symptoms is 18-24 **Some people don't develop signs until their 40's or 50's **Considered adult-onset so may be underdiagnosed in children **Nonsense and frame shift mutations more severe *Bilateral vestibular schwannoma (acoustic neuroma) **Affect almost all patients with NF2 **Tumor that arises from Schwann cells that support and protect nerves with insulation needed to conduct information on 8th cranial nerve **Initial symptoms include tinnitus (ringing in ears), hearing loss, and balance dysfunction **May result in hearing loss in one or both ears *Spinal tumors (>66%) **Include schwannomas that may cause numbness in part of body **Intramedullary tumors such as astrocytoma and ependymoma (5-33%) **Most individuals with spinal cord tumors have more than one *Meningiomas (50%) **Tumor that grows from cells that line the brain and spinal cord in protective sheets called meninges **May be intracranial or spinal **Cause different neurological symptoms depending on location *Ocular involvement (33%) **Cataracts ***Known as juvenile posterior sublenticular opacity ***May impair vision if not removed **Optic gliomas ***Tumors on vision nerve ***May lead to blindness *Other features **Other types of central nervous system tumors **Atypical café-au-lait spots **Cutaneous neurofibromas *Somatic mosaicism **Suspected in individuals with unilateral vestibular schwannoma and multiple other tumors on one side **More difficult to diagnose *Considerably shortened lifespan **Average age of death is 36 years **With improvements in diagnosis, monitoring, and surgery this is changing Diagnosis/Testing Options *Clinical diagnosis **Bilateral VIII nerve mass on CT or MRI (vestibular schwannomas) OR **First degree relative with NF2 and either ***Unilateral 8th nerve mass OR ***Two of the following ****Meningioma ****Glioma ****Schwannoma ****Juvenile posterior subcapsular lenticular opacity *Mutation analysis **Mutations identified in 65-80% of patients with clinical diagnosis **Testing provided by Athena Diagnostics/Mass Gen **Includes SSCP (single stranded conformational polymorphism) **May take up to 6 months for results **Costs about $2700 **Considered appropriate to test unaffected at risk children and adults *Linkage analysis **Appropriate if more than one affected family member **Doesn't work for 50% of patients with de novo mutations **High accuracy because markers are very closely linked *Prenatal testing **Available for fetuses at 50% risk or greater **Can be performed if mutation identified in affected family member **Requires cells obtained from CVS or amniocentesis Management *Currently is no cure or treatment *Early recognition allows for earlier intervention and improved outcome *Begin screening in early teens **ABR and MRI exams for vestibular schwannomas ***Surgery generally successfully preserves hearing is tumors small ***Should begin learning sign language before hearing is lost ***Hearing aids may help preserve hearing early on **Routine complete eye examinations **Routine neurological examinations **Intracranial, cranial nerve, and spinal tumors often slow growing Differential Diagnosis *NF1 **Has Lisch nodules, axillary and inguinal freckling, and plexiform neurofibromas not seen in NF2 **Patients with NF2 do not have mental retardation or learning problems *Unilateral vestibular schwannoma **Accounts for 5-10% of intracranial tumors **Less than 5% are bilateral and associated with NF-2 *Schwannomatosis **Multiple schwannomas without vestibular schwannomas **Develop intracranial, spinal nerve root, or peripheral nerve tumors *Multiple meningiomas **Without vestibular schwannomas **Typically occur in older adults Psychosocial Issues *Feelings of fear, anger, shock, denial over new diagnosis *Difficulty adjusting to loss of hearing *Burden of condition requiring extensive surveillance *Anxiety about possibility of shortened life span *Survivor guilt, transmitter guilt *Support system to help cope with diagnosis Support Resources *National Neurofibromatosis Foundation :95 Pine Street, 16th Floor :New York, NY 10005 :Phone: 800-323-7938 :Web: www.nf.org *Neurofibromatosis, Inc :8855 Annapolis Road, Suite 110 :Lanham, MD 20706-2924 :Phone: 410-461-5213 :Web: www.nfinc.org *The Acoustic Neuroma Association :PO Box 12402 :Atlanta, GA 30355 :Phone: 404-237-2704 :Web: ANAUSA@aol.com References *GeneReviews. "Neurofibromatosis 2" (2002). *"Neurofibromatosis Type 2: Information for Patients and Families." National Neurofibromatosis Foundation brochure. Notes The information in this outline was last updated in 2001. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.